エンドトキシン投与ラットの微小循環障害における白血球および血小板の関与 [in Japanese] Leukocyte and Platelet Adhesion Induce Microcirculatory Disturbance in Endotoxemic Organ Dysfunction [in Japanese]
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敗血症性微小循環障害の発生過程における白血球と血小板の挙動を検討した. 方法 : ラットのLPS1.0 mg/kg投与後1および3時間における腸間膜血流を生体顕微鏡下に直接観察し, 併せて血液算定, tumor necrosis factor α (TNFα), interleukin-6 (IL-6), ALT, BUN, lactateの測定も行った. 結果 : 投与1時間後では後毛細血管細静脈において血管内腔を回転移動 (rolling) する白血球が, 3時間後では接着固定 (adhesion) する白血球と血小板の顕著な接着が観察された. 血液算定では白血球数が1時間後から減少し, 血小板数は3時間後において正常時の1/3以下に減少した (p<0.01). これらは, それぞれ内皮上における接着を反映しているものと考えた. サイトカインはTNFαがLPS投与1時間後に, IL-6が3時間後に最高値を示し, 臓器障害のマーカーとしたALT, lactateは, 15時間後に有意な上昇が確認された (おのおのp<0.01).
Adhesion of leukocytes and platelets to the vascular endothelial cells in endotoxemia induces microcirculatory disturbance that leads to the organ dysfunction. In this study, we investigated the role of leukocyte and platelet in the development of endotoxemic organ dysfunction in rats injected with 1.0 mg/kg of lipopolysaccharide (LPS) and observed the mesenteric microcirculation under an intravital microscope. One hour after the injection of LPS, rolling of leukocytes on the mesenteric endothelial cell surface was conspicuous and their number was significantly increased to that in the control group given the buffer alone (p<0.01). Three hours after the injection, leukocytes appeared to become adherent to the endothelial cell surface, and the adherent leukocytes were significantly increased to the control rats (p<0.05). At this time period, remarkable platelet adhesion to the endothelial cell surface was noted. Conversely, leukocytes in the circulating blood decreased significantly 1 hour after the injection, and the circulating platelet counts were reduced to nearly 1/3 of the initial level 3 hours after the injection (p<0.05). The levels of TNF α and IL-6 in plasma reached their maxima at 1 and 3 hours after the injection, respectively. The results together indicate that leukocytes and platelets adherent to the mesenteric endothelial cell surface may have contributed to the occlusion of the vessels leading to the organ dysfunction. Indeed, the markers selected for the organ damages, i.e. ALT, BUN and lactate were found to be significantly increased 15 hours after the injection.
- Japanese Journal of Thrombosis and Hemostasis
Japanese Journal of Thrombosis and Hemostasis 12(1), 32-38, 2001-02-01
The Japanese Society on Thrombosis and Hemostasis